T lymphocyte
Also known as: T cell, T cells, T-cell, thymocyte, T lymphocytes
Lymphocytes that mature in the thymus and recognise peptide antigens only when displayed on MHC molecules; they orchestrate (CD4 helper), execute (CD8 cytotoxic) and restrain (regulatory) cell-mediated adaptive immunity.
Overview
T cells (thymus-derived lymphocytes) make up ≈ 70–80% of blood lymphocytes, with a CD4:CD8 ratio of about 2:1. Each carries a unique T-cell receptor (TCR) — in ≈ 95% of T cells an αβ heterodimer, in the rest a γδ receptor — generated by V(D)J recombination in the thymus. The TCR is associated with the CD3 complex (γ, δ, ε and ζ chains), which transmits the activation signal; CD3 is the pan-T-cell marker. The co-receptor CD4 binds MHC class II and CD8 binds MHC class I, so helper T cells are "MHC II-restricted" and cytotoxic T cells "MHC I-restricted". Crucially, αβ T cells cannot see free antigen: they recognise short peptide fragments presented in the groove of self-MHC molecules.
Naive T cells (CD45RA⁺, CCR7⁺, CD62L⁺) recirculate through lymphoid organs. Activation needs signal 1 (TCR–peptide–MHC), signal 2 (co-stimulation: CD28 binding B7) and signal 3 (cytokines). TCR signalling raises intracellular calcium, activating calcineurin, which dephosphorylates the transcription factor NFAT, inducing IL-2 and its high-affinity receptor (CD25); IL-2 then drives autocrine clonal expansion (thousands-fold over about a week). Effector cells migrate to infected tissues; most die after the infection, leaving memory T cells (CD45RO⁺).
Functionally, CD4 helper T cells (Th1, Th2, Th17, Tfh) coordinate immune responses through cytokines and CD40L; CD8 cytotoxic T cells kill cells displaying foreign peptide on MHC I; regulatory T cells suppress responses and maintain tolerance. Unconventional T cells — γδ T cells, NKT cells (recognising lipids on CD1d) and MAIT cells — bridge innate and adaptive immunity at barrier sites.
- Location
Thymus (development), paracortex of lymph nodes, PALS of spleen, interfollicular areas of MALT, blood, lymph and tissues.
Parts & subdivisions
- Th1, Th2, Th17 and follicular helper subsets.
- Kill infected, malignant and foreign cells.
- CD4⁺CD25⁺FOXP3⁺ suppressors of immune responses.
- Central, effector and tissue-resident memory subsets.
- TCR–CD3 complexAntigen-binding αβ (or γδ) chains plus CD3 signalling chains.
Anatomy
- Development
T-cell precursors leave the bone marrow for the thymus, where they rearrange TCR genes and undergo positive and negative selection (see thymus).
Function
- Cell-mediated immunity against intracellular pathogens (viruses, intracellular bacteria, protozoa) and tumours.
- Help for B cells (class switching, affinity maturation) and macrophages.
- Killing of infected and transformed cells.
- Regulation of immune responses and maintenance of self-tolerance.
Clinical significance
T-cell deficiency
HIV infection, DiGeorge syndrome and SCID predispose to viral, fungal (Candida, Pneumocystis), mycobacterial and other intracellular infections, and to virus-driven cancers. Live vaccines are dangerous in severe T-cell deficiency.
Drugs targeting T cells
Calcineurin inhibitors (ciclosporin, tacrolimus) block NFAT activation and IL-2 transcription — the backbone of transplant immunosuppression (adverse effects include nephrotoxicity); abatacept (CTLA-4–Ig) blocks co-stimulation; checkpoint inhibitors (anti-PD-1, anti-CTLA-4) unleash anti-tumour T cells at the cost of autoimmune side effects; CAR-T cells are engineered T cells used against B-cell malignancies.
T-cell malignancies
T-lymphoblastic leukaemia/lymphoma (anterior mediastinal mass in adolescent males), mycosis fungoides and Sézary syndrome (cutaneous CD4⁺ T-cell lymphoma), and adult T-cell leukaemia/lymphoma caused by HTLV-1.
Test yourself
The periarteriolar lymphoid sheath (PALS) of the spleen consists mainly of…
- B lymphocytes
- T lymphocytes
- Red cells and macrophages
- Plasma cells
Answer: T lymphocytes
White pulp has a T-cell PALS around central arterioles, with B-cell follicles and a marginal zone at its edge. Red pulp (cords and sinusoids) filters red cells.
In the thymus, positive selection of developing T cells…
- Deletes thymocytes that bind self-antigen strongly
- Occurs in the medulla under the control of AIRE
- Allows survival of thymocytes able to recognise self-MHC, establishing MHC restriction
- Generates the TCR by somatic hypermutation
Answer: Allows survival of thymocytes able to recognise self-MHC, establishing MHC restriction
Positive selection takes place in the cortex on cortical epithelial cells: double-positive thymocytes whose TCR weakly recognises self-peptide–MHC survive (MHC restriction, CD4/CD8 commitment); the rest die by neglect. Negative selection (medulla, AIRE) removes strongly self-reactive cells.
MHC class II molecules…
- Are expressed on all nucleated cells
- Present endogenous peptides to CD8 T cells
- Present exogenous peptides to CD4 T cells and are expressed mainly on antigen-presenting cells
- Consist of a heavy chain associated with β2-microglobulin
Answer: Present exogenous peptides to CD4 T cells and are expressed mainly on antigen-presenting cells
Class II (HLA-DP, -DQ, -DR; α and β chains) is expressed on dendritic cells, macrophages, B cells and thymic epithelium and presents peptides from endocytosed (exogenous) proteins to CD4 T cells. Class I (heavy chain + β2-microglobulin) is on all nucleated cells and presents to CD8 cells.
Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.